Our long range goal is to understand the mechanisms by which respiratory virus infections cause airway hyperreactivity and exacerbate asthma. Although the mechanisms of airway hyperresponsiveness associated with respiratory viral illnesses and not established, present evidence strongly suggests the virus effects on respiratory structure, immune function and the inflammatory response are important to the pathogenesis of bronchial hyperreactivity and asthma. From observations with human leukocytes, parainfluenza-3 infected guinea pigs, and patients experimentally infected with rhinovirus, we hypothesize that a major mechanism for virus induced airway hyperresponsiveness is enhanced activity of those cells which participate in airway inflammation. In examining this hypothesis, we hope to define the elements of a major mechanism of virally induced asthma through human experiments which will be complemented by more extensive and established animal correlates. Specifically, bronchoalveolar lavage (BAL) will be used to establish the effect of rhinovirus 16 infection on pulmonary mast cell mediator release, alveolar macrophage function, and air space lymphocytes to promote bronchial inflammation and hyperreactivity in humans. Studies in parainfluenza I infected rats will establish the relationship of airway inflammation towards a persistence of bronchial hyperreactivity and the development of late phase asthma. In parainfluenza-3 infected guinea pigs, experiments will establish the role of sensory neuropeptides and IgG1 and I&E-dependent mediator release in airway responsiveness during the acute infection. Finally, the biochemical properties of the guinea pig pulmonary mast cell beta-adrenergic receptor will be characterized along with changes associated with a parainfluenza-3 infection. From these experiments we will learn the biology of the airway response to viral infections and establish the mechanisms which cause airway hyperreactivity and participate in asthma pathogenesis. Further, we hope to show that no single cell, or abnormality, is exclusively responsible for the generation of airway inflammation and hyperreactivity in viral respiratory infections. Rather, viral respiratory illnesses cause airway injury and hyperresponsiveness through a complex interaction of direct cytopathic properties of the virus and an integrated effect on respiratory cells and tissues which rssults in inflammation and thus bronchial hyperresponsiveness and obstruction.